MHC II-restricted presentation of soluble antigen by naïve B cells is impaired upon engagement with membrane-associated antigen: A potential mechanism to mitigate autoreactivity.

T cell tolerance to self can prevent self-reactive B cells from mounting effective autoimmune responses by limiting their available help. However, tolerance may be compromised during infection if small amounts of soluble cross-reactive pathogen antigens containing functional T cell epitopes are released for capture by activated B cells. Here, we assess this scenario and show that naïve B cells engaged and activated by membrane-bound antigens lacking T helper epitopes are impaired in their ability to capture and present additional soluble antigens containing T helper epitopes. This limits their ability to acquire help from cognate CD4+ T cells required for effective antibody responses. Failure to capture and present soluble antigen is due to IgM and IgD downregulation when engaged with membrane-bound antigen. Interestingly, IgG+ B cells are not similarly constrained and effectively capture soluble antigens. Our findings suggest control of naïve B cell tolerance partially depends on efficient receptor downregulation upon antigen engagement.